The Pioneer platform: A novel approach for selection of
selective anti-cancer cytotoxic activity in bacteria through
co-culturing with engineered human cells

J 2023

The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells

GARLAND, Gavin D; Kiran R PATIL; Suzanne Dawn TURNER a Anne E WILLIS

Základní údaje

Originální název

The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells

Autoři

GARLAND, Gavin D; Kiran R PATIL; Suzanne Dawn TURNER a Anne E WILLIS

Vydání

Plos one, San Francisco, Public Library of Science, 2023, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10606 Microbiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/23:00133375

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

REDOX PROTEIN AZURIN; COLICIN-M; CHLORAMPHENICOL ACETYLTRANSFERASE; MAMMALIAN-CELLS

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 7. 2024 14:21, Mgr. Eva Dubská

Anotace

V originále

Most of the small-molecule drugs approved for the treatment of cancer over the past 40 years are based on natural compounds. Bacteria provide an extensive reservoir for the development of further anti-cancer therapeutics to meet the challenges posed by the diversity of these malignant diseases. While identifying cytotoxic compounds is often easy, achieving selective targeting of cancer cells is challenging. Here we describe a novel experimental approach (the Pioneer platform) for the identification and development of 'pioneering' bacterial variants that either show or are conduced to exhibit selective contact-independent anti-cancer cytotoxic activities. We engineered human cancer cells to secrete Colicin M that repress the growth of the bacterium Escherichia coli, while immortalised non-transformed cells were engineered to express Chloramphenicol Acetyltransferase capable of relieving the bacteriostatic effect of Chloramphenicol. Through co-culturing of E. coli with these two engineered human cell lines, we show bacterial outgrowth of DH5 alpha E. coli is constrained by the combination of negative and positive selection pressures. This result supports the potential for this approach to screen or adaptively evolve 'pioneering' bacterial variants that can selectively eliminate the cancer cell population. Overall, the Pioneer platform demonstrates potential utility for drug discovery through multi-partner experimental evolution.

Citovat

GARLAND, Gavin D; Kiran R PATIL; Suzanne Dawn TURNER a Anne E WILLIS. The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells. Plos one. San Francisco: Public Library of Science, 2023, roč. 18, č. 6, s. 1-15. ISSN 1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0286741.

@article{2368561,
   author = {Garland, Gavin D and Patil, Kiran R and Turner, Suzanne Dawn and Willis, Anne E},
   article_location = {San Francisco},
   article_number = {6},
   doi = {https://doi.org/10.1371/journal.pone.0286741},
   keywords = {REDOX PROTEIN AZURIN; COLICIN-M; CHLORAMPHENICOL ACETYLTRANSFERASE; MAMMALIAN-CELLS},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos one},
   title = {The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells},
   url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0286741},
   volume = {18},
   year = {2023}
}

TY  - JOUR
ID  - 2368561
AU  - Garland, Gavin D - Patil, Kiran R - Turner, Suzanne Dawn - Willis, Anne E
PY  - 2023
TI  - The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells
JF  - Plos one
VL  - 18
IS  - 6
SP  - 1-15
EP  - 1-15
PB  - Public Library of Science
SN  - 19326203
KW  - REDOX PROTEIN AZURIN
KW  - COLICIN-M
KW  - CHLORAMPHENICOL ACETYLTRANSFERASE
KW  - MAMMALIAN-CELLS
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0286741
N2  - Most of the small-molecule drugs approved for the treatment of cancer over the past 40 years are based on natural compounds. Bacteria provide an extensive reservoir for the development of further anti-cancer therapeutics to meet the challenges posed by the diversity of these malignant diseases. While identifying cytotoxic compounds is often easy, achieving selective targeting of cancer cells is challenging. Here we describe a novel experimental approach (the Pioneer platform) for the identification and development of 'pioneering' bacterial variants that either show or are conduced to exhibit selective contact-independent anti-cancer cytotoxic activities. We engineered human cancer cells to secrete Colicin M that repress the growth of the bacterium Escherichia coli, while immortalised non-transformed cells were engineered to express Chloramphenicol Acetyltransferase capable of relieving the bacteriostatic effect of Chloramphenicol. Through co-culturing of E. coli with these two engineered human cell lines, we show bacterial outgrowth of DH5 alpha E. coli is constrained by the combination of negative and positive selection pressures. This result supports the potential for this approach to screen or adaptively evolve 'pioneering' bacterial variants that can selectively eliminate the cancer cell population. Overall, the Pioneer platform demonstrates potential utility for drug discovery through multi-partner experimental evolution.
ER  -

GARLAND, Gavin D; Kiran R PATIL; Suzanne Dawn TURNER a Anne E WILLIS. The Pioneer platform: A novel approach for selection of selective anti-cancer cytotoxic activity in bacteria through co-culturing with engineered human cells. \textit{Plos one}. San Francisco: Public Library of Science, 2023, roč.~18, č.~6, s.~1-15. ISSN~1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0286741.

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